EP2703817A1 - Control de fluides sur puce avec des éléctrodes - Google Patents

Control de fluides sur puce avec des éléctrodes Download PDF

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Publication number
EP2703817A1
EP2703817A1 EP12182729.9A EP12182729A EP2703817A1 EP 2703817 A1 EP2703817 A1 EP 2703817A1 EP 12182729 A EP12182729 A EP 12182729A EP 2703817 A1 EP2703817 A1 EP 2703817A1
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EP
European Patent Office
Prior art keywords
electrode
working electrode
fluid
reference electrode
fluid sample
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP12182729.9A
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German (de)
English (en)
Inventor
Fredrik Jansson
Magnus Molin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Celoxio AB
Original Assignee
Celoxio AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Celoxio AB filed Critical Celoxio AB
Priority to EP12182729.9A priority Critical patent/EP2703817A1/fr
Priority to ES13756177.5T priority patent/ES2644613T3/es
Priority to PCT/EP2013/068201 priority patent/WO2014033329A1/fr
Priority to EP13756177.5A priority patent/EP2893348B1/fr
Priority to US14/425,387 priority patent/US10309926B2/en
Publication of EP2703817A1 publication Critical patent/EP2703817A1/fr
Withdrawn legal-status Critical Current

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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • F04B43/043—Micropumps
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44791—Microapparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427—Electrowetting

Definitions

  • the present invention relates to devices for controlling movement of fluid samples in microfluidic chips and to a method for controlling or manipulating a fluid flow through channels of such microfluidic chips.
  • the microfluidic chips may be used in biotechnological, diagnostical and pharmaceutical applications.
  • Microfluidics relates to a multidisciplinary field comprising physics, chemistry, engineering and biotechnology that studies the behavior and flow of fluids at nano and microliter scale inside open or closed microchannels.
  • Microfluidics has enabled the development of so-called 'lab-on-a-chip' devices and systems that can process microliter and nanoliter volumes of sample fluid, and perform highly complex and sensitive analytical measurements.
  • 'Lab-on-a-chip' indicates the scaling of single or multiple laboratory processes down to a chip-format, which is only millimeters to a few centimeters in size.
  • Microfluidic-based analysis chips and microfluidic-based diagnostic test chips are used for a variety of biotechnological and diagnostic applications, such as nucleic acid detection, characterization, separation, sizing, and typing; cell manipulation and sorting; biomarker detection; microbial pathogen detection; and miniaturization of chemical synthesis.
  • Microfluidic-based chips offer many advantages over traditional macro-sized counterparts: Easy handling (less hands-on-time, and less sample and reagents are required) and rapid test results (shorter analysis times).
  • Easy handling less hands-on-time, and less sample and reagents are required
  • rapid test results shorter analysis times.
  • the shorter analysis time and easy handling of microfluidic chips is attractive for diagnostic applications because it enables rapid bedside and doctor's office tests, offering the advantage of rapid test result that can be shared with the patient right away.
  • diagnostic applications require a strict control of the sample fluid flow within the chip in order to ensure the required accuracy and reproducibility of the analysis/test.
  • operations such as mixing; incubation; separation; and detection are performed within the chip, which demands firm control of the sample fluid flow in terms of timing, volumes and flow rates.
  • Time gates can be designed to slow down or stop the flow of a predetermined volume for a predetermined time and channels can be designed to have the right capillary force to drive the flow at a predetermined flow rate.
  • variable composition and viscosity of biological samples puts up a major challenge to microfluidic assay development.
  • Typical biological samples include e.g. saliva, urine, serum, plasma and whole blood, and they vary in composition and viscosity from individual to individual as well depending on when the sample was taken. These variations, along with variations in the surface properties of the microfluidic chips, causes variations in timing, volumes and flow rates and can thereby negatively affect the reproducibility of diagnostic microfluidic-based tests.
  • a wettability switch allow for manipulation of a solid surface's ability to maintain contact with a liquid.
  • the wettability is determined by a force balance between adhesive and cohesive forces when the solid switch surface is in contact with the liquid. Adhesive forces between the solid and the liquid cause a liquid drop to spread across the switch surface. Cohesive forces within the liquid cause the liquid drop to ball up and avoid contact with the switch surface.
  • the force balance can be manipulated through various influences such as light, temperature, chemistry, electrochemistry or electric field. Within the area of microfluidics some kind of electronic influence is preferred due to its rapid actuation and low interference with the fluid.
  • electrochemical electrowetting where a voltage in the order of one volt is applied between a working electrode and a reference electrode, in electrical contact with each other through an electrolytical fluid, forming an electrochemical double layer at the surface of the work electrode that increases its wettability.
  • Another technology used for electronically altering the wettability of a surface is electrowetting on dielectric, where tens to hundreds of volts are applied between a working electrode and a reference electrode, electrically isolated from each other, forming a strong electric field that forces the droplet down towards the isolated work electrode surface.
  • a further technology used for electronically altering the wettability of a surface is electrowetting with ion-doped conducting polymers, where a few volts are applied between a working electrode doped with polar ions, having a hydrophobic and a hydrophilic end, and a reference electrode, making the polar ions shifting orientation and thus shifting the wettability of the work electrode surface.
  • electrochemical electrowetting is preferred in its simplicity, amongst others due to a greater wettability change and a better long term stability compared to electrowetting using ion-doped conducting polymers and due to a low voltage need and cost effectiveness compared to electrowetting on dielectric.
  • microfluidic chips having a reference electrode placed in the beginning of a flow path (microfluidic channel) followed by one or a few work electrodes downstream the flow path.
  • the working electrodes are typically hydrophobic thus stopping the fluid in their natural state, but turn hydrophilic and let the fluid pass when a voltage is applied.
  • a major drawback with the electrochemical electrowetting microfluidics technology is that the speed of the fluid flow front may rapidly decrease with the distance travelled along the flow path. About one centimetre into the channel, the electrically activated flow may more or less have ceased, thereby impeding activation of a switch.
  • the research team conclude that when applying a voltage between the working electrode and the reference electrode the fluid front starts to move along the working electrode. However, they conclude that the speed of the fluid front decreases with the distance travelled in the channel and that the movement finally cease. In fact the research team concludes that the fluid front never reaches through the about 18 mm long channel.
  • the research team conclude that the decrease of the flow rate and final cease of the flow are due to the viscous resistance, which is said to increase linearly with the distance travelled.
  • the research team further conclude that by working with microfluidic chips of about 10x10 mm this limitation might be acceptable.
  • the channel length limitation is actually shorter than 1 cm when using the working electrode(s) for driving a flow within the channel.
  • flow velocities of tens of millimetre per minute are typically required. Due to the rapid decrease of the flow velocity, the velocity of the fluid front is below what is required already a few millimetres into the channel.
  • the channel length limitation is for practical reasons also limiting the number of working electrodes that are possible to place along the flow path, given a certain minimal working electrode size possible to produce cost effectively (for instance the smallest working electrode possible to produce with a metal sputter mask instead of photolithography).
  • multiple operations according to above need to be performed with firm and fine-tuned flow control.
  • a limited number of fairly large working electrodes, relative to the length of the channel is thus limiting the number of operations and the possibility of fine-tuned flow control.
  • An object of the present invention is to wholly or partly overcome the above drawbacks of the prior art and to provide an alternative to the above technique.
  • the inventors of the present invention have surprisingly found that the above mentioned limitations of the prior art not only depend on the viscous resistance, but is also depending on the design and placement of the electrodes, and that a new electrode setup may overcome the above mentioned limitations of the prior art.
  • a device for controlling movement of a fluid sample along a flow path comprises a working electrode arranged to contact the fluid sample when the fluid sample moves along the flow path, and a reference electrode arranged to contact the fluid sample when the fluid sample moves along the flow path. At least a portion of the reference electrode is arranged abreast of or downstream at least a portion of the working electrode.
  • a method for transportation of a fluid sample along a flow path comprises the steps of providing a working electrode arranged to contact the fluid sample when the fluid sample moves along the flow path, and providing a reference electrode arranged to contact the fluid sample when the fluid sample moves along the flow path. At least a portion of the reference electrode is arranged abreast of or downstream at least a portion of the working electrode.
  • the method may further comprise the steps of providing a fluid sample at one end of the flow path, and applying a voltage between the working electrode and the reference electrode. The applied voltage alters the wettability of the working electrode surface and thereby promotes advancement of the fluid front across the working electrode surface, along the flow path.
  • the present invention is based on the idea that by arranging at least a portion of a reference electrode abreast of or downstream an upstream end portion of a working electrode (which may be the first of several working electrodes along the flow path in the direction of the flow), the present invention may preserve the working electrode(s)'s capacity to change wettability along the flow path and may thereby overcome the channel length limitation of the prior art.
  • the fluid sample may be transported and accurately controlled, with respect to e.g. timing, volumes and flow rates, over greater distances compared to prior art. The greater distance over which the fluid sample can be controlled enables, amongst others:
  • the present invention may overcome the above mentioned limitations of the prior art and may have the capability to handle microliter volumes of sample fluid with the firm control of timing, volumes and flow rates required for many applications within medical diagnostics.
  • Electrode should be understood any electrically connectable surface that is adapted to be in electrical contact with the sample fluid and an external power supply.
  • the electrodes may for example be arranged at any surface facing the flow path.
  • a working electrode may be defined as an electrode that changes, or is adapted to change, wettability (or hydrophobicity/hydrophilicity) upon application of a voltage between the working electrode and a reference electrode.
  • a reference electrode may be defined as an electrode acting as a counter (or auxiliary) electrode or a reference electrode of a working electrode upon application of a voltage between the working electrode and the reference electrode. It may also be a combined counter electrode and reference electrode. The electrical potential difference may be generated by an external voltage supply.
  • the working electrode and the reference electrode being arranged to contact the fluid sample when said fluid sample moves along the flow path means that the electrodes are so arranged along the flow path that they contact the fluid sample when the device of the invention is in use for controlling movement of a fluid.
  • the reference electrode and the working electrode together may form a first pair of electrically related electrodes.
  • the reference electrode and the working electrode might as well form parts of different electrode pairs, such as a second and a third pair, respectively.
  • the device may comprise a plurality of working electrodes and/or a plurality of reference electrodes.
  • the electrodes may also be arranged in pairs, or groups of three or more electrodes.
  • the flow path may be a longitudinal portion of the device along which portion the front surface of the fluid sample moves during use, thereby causing a subsequent flow or movement of the fluid sample.
  • the flow path may comprise an inlet, adapted to receive a fluid and supply it to the flow path, and an outlet adapted to outlet a fluid (such as for example the fluid sample, or air).
  • a fluid such as for example the fluid sample, or air.
  • the fluid may flow from the upstream end portion of the flow path towards the downstream end portion. This direction may also be referred to as the flow direction.
  • the flow path may for example be a channel or a tube, fully or partly defined by portions of the electrodes or other suitable materials.
  • Controlling movement of the fluid comprises actuating and stopping the flow, which may be enabled by applying and not applying, respectively, a voltage between the working electrode and the reference electrode.
  • the controlling of the movement may also include varying the velocity of the fluid flow, for example by increasing or decreasing the applied voltage.
  • fluid should, in the context of the present invention, be understood any electrically conductive liquid, or electrolyte. This could for example include bodily fluids such as saliva, urine, serum, plasma, and full blood.
  • a portion of a reference electrode being arranged abreast of a portion of a working electrode means that a portion of the reference electrode and a portion of the working electrode both intersect a common plane that is perpendicular to the direction of fluid flow, or movement, along the flow path.
  • a portion of a reference electrode may also be arranged downstream of a portion of a working electrode. Downstream from a point along the flow path should, in this context, be understood as the part of the fluid path located after that point in the direction of flow, or movement, of a fluid when a device of the invention is in use for controlling movement of a fluid. Upstream from a point along the flow path should, in this context, be understood as the part of the fluid path located before that point in the direction of flow, or movement, of a fluid when a device of the present invention is in use for controlling movement of a fluid.
  • the working electrode may be a plane electrode.
  • a plane electrode is preferably an electrode having a lateral extension that is larger than the thickness of the electrode, such as a lead deposited on a substrate.
  • This embodiment is advantageous in that it may enable the electrode material to be applied to a surface of the flow path by sputtering, evaporation, screen printing, or other deposition techniques known in the art.
  • the electrodes may advantageously be defined by patterning methods that are used for example in the electronics industry.
  • the working electrode and the reference electrode may extend in separate planes, or surfaces.
  • Each plane may for example be defined by a wall of a channel, correspondingly, wherein the working electrode may be arranged at a first wall, such as the bottom of the channel, and wherein the reference electrode may be arranged at a second wall, such as the opposing top wall (roof) of the channel.
  • This embodiment is advantageous in that it may facilitate production of the electrodes, which may be manufactured in separate processes. Being able to use separate production methods for the working electrode and the reference electrode may be an advantage for example in the case when the working electrode and the reference electrode do not comprise the same material, or require different handling.
  • the working electrode may be a longitudinal electrode in relation to the flow path.
  • a longitudinal electrode may, preferably, be an electrode having an extension in the flow direction (length) that is larger than the extension in a direction perpendicular to the fluid flow (width).
  • the length of the electrode may for example be essentially equal to the length of the channel.
  • the device may comprise a plurality of working electrodes and reference electrodes. Longitudinal electrodes may be advantageous in that they may allow for the fluid sample to be actively transported over long distances along flow path.
  • the device comprises at least two working electrodes and/or at least two reference electrodes which are consecutively arranged along the flow path. This may reduce the total electrode area and may, advantageously, allow for an individual application of voltage.
  • a separate control of each or a group of electrodes may increase the control of the movement of the fluid during use of the device (e.g. a separate working electrode used as a flow gate/stop or several consecutively arranged working electrodes used for achieving a pulsed flow where the activation (application of a voltage) of each working electrode represents one flow puls).
  • the device may comprise at least two interdigitated electrodes.
  • a work electrode may be interdigitated with a reference electrode or a second work electrode.
  • a reference electrode may be interdigitated with another reference electrode.
  • the device may comprise at least one reference electrode and at least two interdigitated working electrodes (interdigitated into each other).
  • This embodiment is advantageous in that it may enable a fine-tuned pulsed flow with only one electrical contact pad for the first interdigitated working electrode, one electrical contact pad for the second interdigitated working electrode and one contact pad for the reference electrode.
  • the sample fluid may pass the first "finger" of the first interdigitated working electrode, but may stop at the beginning of the first "finger" of the second interdigitated working electrode, since it may not yet be activated (i.e. no voltage applied on the second interdigitated working electrode).
  • the voltage between the first interdigitated working electrode and the reference electrode may be switched off.
  • the sample fluid may pass the first "finger" of the second interdigitated working electrode, but may stop at the beginning of the second "finger” of the first interdigitated working electrode, since it may not yet be activated.
  • the voltage between the second interdigitated working electrode and the reference electrode may be switched off.
  • a fine-tuned pulsed flow may be achieved over long distances with just three contact pads as described above. This is advantageous in that the flow can be controlled reproducibly and in that mean flow rate can be accurately controlled.
  • the flow path may be a channel.
  • the channel may be defined by one or several walls, such as a bottom wall, two sidewalls, and a top wall.
  • the channel may also have a circular, rectangular, or triangular cross section, or any other suitable shape that allows a flow of the fluid sample.
  • the device may further comprise a fluid reservoir arranged to receive and accommodate the fluid sample, and from which the fluid front moves along the flow path.
  • the reservoir may for example be a container or void that may communicate with the flow path such that a fluid sample can be supplied to the flow path.
  • the working electrode and/or the reference electrode may comprise at least a surface that is biocompatible and electrically conducting. It may also be possible to modify the wettability of the surface by altering an applied potential. Examples of such materials may include noble metals, carbon and allotropes of carbon, such as gold, platinum, iridium, osmium, silver, palladium, carbon, graphite, graphene, and fullerenes. Other examples may include electronically conducting polymers.
  • the working electrode and/or the reference electrode may comprise a structured surface adapted to contact the fluid sample during use of the device.
  • the structured surface may for example be a micro- and/or nanostructured surface.
  • This embodiment is advantageous in that the structured surface may increase the hydrophobicity of the surface of the working electrode in its inactivated state (i.e. with no voltage applied). It may also increase the hydrophobicity of the reference electrode. Since the fluid front may tend to stop propagating as it encounters a hydrophobic surface, this embodiment may enable an improved ability of stopping, and thereby controlling, the fluid flow.
  • the device may be adapted to apply a potential difference between the working electrode and the reference electrode.
  • the voltage between the electrodes may be chosen such that a change of wettability may be obtained without affecting the fluid sample such that the measuring or analysis result is risked.
  • the voltage may for example be in the range of -5 V to +5 V, and preferably in the range of -1.3 to +1.3 V.
  • FIG. 1 there is shown a schematic view of a device for movement of a fluid sample along a flow path 1 according to an embodiment of the present invention.
  • the device of the present embodiment comprises a channel 1 defined by a bottom, a roof, and two sidewalls.
  • a longitudinal, plane working electrode 2 is arranged on a surface of the bottom of the channel 1 facing the fluid.
  • the roof is provided with two longitudinal, plane reference electrodes 3 arranged on a surface of the roof extending along, and in parallel with, the working electrode 2. Both electrodes are arranged to electrically contact the fluid sample as it moves along the channel 1.
  • the working electrode 2 may comprise a sputtered gold layer and be provided with contacts 5 for application of a voltage.
  • the reference electrode 3 may be a silver electrode that is screen printed on a plastic film, also comprising a contact area 4 for electrical connection.
  • the bottom and the roof of the channel 1 may be joined by an intermediate adhesive tape 8, defining the channel 1 in which the fluid sample may flow during use.
  • the device preferably comprises a sample loading hole 10 communicating with a fluid reservoir 6 arranged to receive and accommodate the fluid sample.
  • the fluid reservoir 6 may communicate with the channel 1 such that the fluid sample may be supplied to the channel 1.
  • a fluid outlet hole 11 is arranged such that e.g. air may be evacuated from the channel as the fluid sample is introduced in the channel 1.
  • the device may further comprise through connections and contact pads 4,5 for connecting the electrodes to for example an external power supply to enable the working electrode 2 to act as a wettability switch.
  • a fluid sample volume of for example 20 ⁇ l is applied to the upstream end portion of the channel 1 via the inlet and the fluid reservoir 6.
  • a voltage is applied between the working electrode 2 and the reference electrode 3, for example 1.2 V, the wettability of the working electrode 2 is changed to its more hydrophilic state, inducing a movement of the fluid front.
  • an actuation of the fluid flow may be obtained by applying an electrical voltage between the electrodes 2,3.
  • the working electrode 2 may then switch to a more hydrophilic state and thereby enable the fluid to pass the electrodes.
  • a fluid flow may be stopped by from passing the working electrode 2 by removing the electrical voltage. Thereby a control of the movement, wherein the flow may be both actuated and stopped, is enabled.
  • Electrodes 2,3 may be provided with a structured surface comprising micro- and/or nanostructures which may increase the hydrophobic nature of the surfaces, at least in their initial, non-activated state.
  • the microstructures and/or nanostructures may for example include the geometrical form of hills, ridges, paraboloids, pillars, or trenches.
  • Figure 2 is a top plan view illustrating another embodiment of a device for movement of a fluid sample along a flow path 1, having one longitudinal plane reference electrode 3 (outline indicated by dashed lines) arranged on a surface of the roof and extending along, and in parallel with, the channel 1.
  • a series of working electrodes 2 are arranged on the bottom of the channel 1 and connected to an external power supply in order to enable a change of wettability.
  • the wettability of the working electrodes 2 may be individually controlled (e.g. for the use as consecutively arranged flow gates/stops in a hydrophilic capillary channel).
  • an embodiment of the device may also comprise interdigitated work electrodes 2.
  • two longitudinal work electrodes 2, extending along the bottom surface of the channel 1 may share a common interdigitated area defined by transverse fingers consecutively arranged along the channel 1.
  • the reference electrode 3 may be placed along the roof surface of channel 1.
  • Each of the two interdigitated working electrodes 2 may have one separate contact area 5.
  • the wettability of the two interdigitated working electrodes 2 may be individually controlled (e.g. for the use as consecutively arranged flow gates/stops in a hydrophilic capillary channel).
  • Figure 4 illustrates a further embodiment of the present invention, in which a portion of a reference electrode 3 (outlined by dashed lines) is arranged abreast of a portion of a working electrode 2.
  • the working electrode 2 may be arranged at the bottom surface, and the reference electrode 3 at roof of the channel 1.
  • the working electrode 2 and the reference electrode 3 may share a common plane, or surface.
  • one longitudinal working electrode 2 is arranged at the bottom surface of the channel 1, in between and parallel with two longitudinal reference electrodes 3.
  • Figure 6 shows an exploded view of a device according to an embodiment of the present invention.
  • a bottom layer 2 is coated with gold constituting the working electrode 2.
  • the gold coated side of the bottom layer 2 defines the bottom of the channel 1.
  • a self-adhesive spacer tape 8 is arranged, defining the walls of the channel 1 and the reservoir volume 6.
  • a polymer film 9, onto which a silver reference electrode 3 is screen printed, is arranged on top of the stacked layers.
  • the screen printed side of the polymer film 9 defines the roof of the channel 1.
  • the electrode layers are connected to contact pads 4,5 for enabling electrical connection to an external power supply.
  • Figure 7 shows a top plan view of the embodiment of figure 6 , wherein the outer boundary 12 and the inner boundary 13 of the reference electrode 3, the channel side walls 14, and an electrical through connection 15 between the reference electrode 3 and the contact area 4 for the reference electrode 3 are indicated by dashed lines.
  • the device according to the present invention may be used in for example biotechnological applications, such as micro-total analysis systems ('lab-on-a-chip' systems); micro-factories and chemical or biochemical micro-plants; miniaturization of chemical synthesis, biosensors; rapid DNA separation and sizing; cell manipulation and sorting; food analysis; detection of biological warfare, and diagnostic applications, such as biomarker detection; genetic analysis, typing and fingerprinting; microbial pathogen detection, and in various pharmaceutical applications.
  • biotechnological applications such as micro-total analysis systems ('lab-on-a-chip' systems); micro-factories and chemical or biochemical micro-plants; miniaturization of chemical synthesis, biosensors; rapid DNA separation and sizing; cell manipulation and sorting; food analysis; detection of biological warfare, and diagnostic applications, such as biomarker detection; genetic analysis, typing and fingerprinting; microbial pathogen detection, and in various pharmaceutical applications.
  • the channels 1 described with reference to Figures 1-7 have a rectangular enclosing surface
  • the channel 1 of the device is not limited to such a shape and may, for instance, have a circular cross section, or only two or three walls. Consequently, although the working electrodes 2 and the reference electrodes 3 described in the present application are plane electrodes, it will be appreciated that the electrodes 2,3 may have other shapes adapted to the shape of the inside of the channel 1 into which such electrodes 2,3 are intended to be arranged.
  • the embodiments are not limited to having the reference electrode 3 arranged at the roof and the working electrode 2 at the bottom of the channel 1.
  • the electrodes might as well be arranged the other way around, i.e. the reference electrode 3 being arranged at the bottom and the working electrode 2 at the roof of the channel 1.
  • One or several of the electrodes might also be arranged at the sidewall(s).
  • microfluidic chips were used for fluid flow tests to characterize electrowetting actuated fluid flow rate and length.
  • Microfluidic chips were constructed by assembly of the following: a gold coated microscopic slide 2, a 73 ⁇ m self-adhesive spacer tape 8, a cyclo olefin polymer (COP) plastic film 9 as is, or with a screen printed silver/silver chloride reference electrode 3 facing the microchannel 1.
  • COP cyclo olefin polymer
  • FIG. 6 shows the composition of the different layers of the microfluidic chips where the gold coated slide 2 make up the floor, the spacer tape 8 the walls, and the COP film 9 (including the reference electrode 3) the roof of the microfluidic channel 1.
  • the microfluidic channel 1 or flow path 1 is here defined by a plane metallic electrode at the bottom, spacer tape 8 walls of the spacer tape 8 at the sides, and reference electrode 3 roof portions of the reference electrode 3 and a plastic film 9 roof portion of the plastic film 9.
  • Channel geometry was created by laser cutting the spacer tape creating a 2 mm wide channel 1 with a height of 73 ⁇ m, and length of 63 mm.
  • a circular hole 10 allowing sample loading, and one rectangular 0.5x2 mm hole 11 for air outlet was created by laser cutting the COP film 9.
  • the COP film 9 i.e. the roof
  • a silver/silver chloride composition for screen printing was used for screen printing the reference electrode 3.
  • chip configuration 1 a 0.38 mm thick silver wire was used as reference electrode 3.
  • the chips were then assembled by allowing self-adhesive spacer tape 8 to adhere to the gold coated slides 2 followed by placement of the COP film 9 (with or without screen printed silver/silver chloride electrode 3) such that the sample loading 10 and air inlet holes aligned with the microchannel geometry of the adhesive.
  • Figure 6 is an exploded view showing a chip assembled according to configuration 2, comprising a working or work electrode 2, i.e. gold coated slide, an adhesive layer 8, and a plastic film 9 with screen printed silver/silver chloride forming the reference electrode 3.
  • Figure 7 is a top view showing a sample loading hole 10, an outer and inner boundary of the silver or reference electrode 3, a channel 1 side wall, and a contact areas 4, 5 for the reference and working electrodes 3, 2.
  • the fluid may eventually stop before halfway through the channel 1, maybe due to lowering of the voltage potential across the fluid front as the resistance of fluid contained within the channel 1 increases with fluid flow length. After electrowetting actuated flow ceased (approximately 10 mm) the fluid continues to travel to the point where the so called viscous resistance counteracts the capillary force.
  • the working electrode 2 did not experience any fluid flow length limitations, i.e. the flow seems not to be affected by the flow path length, and flow rate dropped only marginally across the 63 mm long channel 1, and seldom below 1.8 mm/s.
  • having the reference electrode 3 and working electrode 2 arranged along the flow path 1 to contact the fluid sample along the path a controlled and reliable flow of the fluid sample may be obtained.
  • chip configuration 2 presents a greater resistance to capillary flow compared to configuration 1 (without a screen printed reference electrode 3).
  • the arrangement of the reference and working electrode 2 of the device according to the embodiment described herein may prevent loss/lowering of the voltage potential across the fluid front, why fluid flow length limitations may be, if not completely abolished, at least substantially advanced, and not markedly limited by the viscous resistance.
  • Microfluidic chips were constructed by assembly of the following:
  • Chip layers were assembled as described in Example 1. 20 ⁇ l bovine serum was used as fluid sample and was applied to the sample loading hole 10 of each chip using a micropipette. The fluid sample was allowed to settle in the sample loading hole for 30 seconds, to allow it to wet the COP film 9 edges bordering the loading hole 10, where after minus (-) 1.2 V was applied to the working electrode 2 (i.e. the gold surface), to promote electrowetting and the subsequent flow of fluid pass the electrode surface. Voltage was thereafter applied according to a pre-programmed scheme (see Table 1).
  • Chips according to configuration 1 (with upstream, silver wire electrode) and configuration 2 (with longitudinal electrodes or electrodes arranged along the flow path 1) as described in Example 1 were used for the experiment.
  • Short 1 second pulses with minus (-) 1.2 V (followed by a 30 second waiting period) were applied repeatedly, to allow discrete flow rates along the entire distance travelled by the fluid to be measured.
  • Figure 8 showing a diagram of the flow rate against microchannel flow length. Results are shown for activated flow for a longitudinal reference electrode, activated flow for an upstream reference electrode, passive flow for a longitudinal reference electrode and passive flow for an upstream reference electrode.
  • Chips having a reference electrode 3 placed parallel to, and at constant distance from, the working electrode 2 did not experience any fluid flow length limitations, and flow rate dropped only 5 fold at most and plateaued at 100 mm/min at the end of the 63 mm long channel 1, which is in agreement with the results obtained in the experiment described in Example 1 (where minimal flow was 1,8 mm/s, which is equal to 108 mm/min).
  • placing the reference electrode 3 of microfluidic systems according to the current invention substantially improves microfluidic flow rates and pushes the boundaries for fluid flow length to a point where the development of a variety of microfluidic applications is enabled and such microfluidic chips became realizable.
EP12182729.9A 2012-09-03 2012-09-03 Control de fluides sur puce avec des éléctrodes Withdrawn EP2703817A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP12182729.9A EP2703817A1 (fr) 2012-09-03 2012-09-03 Control de fluides sur puce avec des éléctrodes
ES13756177.5T ES2644613T3 (es) 2012-09-03 2013-09-03 Control en chip de fluidos usando electrodos
PCT/EP2013/068201 WO2014033329A1 (fr) 2012-09-03 2013-09-03 Contrôle sur puce de liquides à l'aide d'électrodes
EP13756177.5A EP2893348B1 (fr) 2012-09-03 2013-09-03 Control de fluides sur puce avec des éléctrodes
US14/425,387 US10309926B2 (en) 2012-09-03 2013-09-03 On chip control of fluids using electrodes

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EP12182729.9A EP2703817A1 (fr) 2012-09-03 2012-09-03 Control de fluides sur puce avec des éléctrodes

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018106750A1 (fr) * 2016-12-08 2018-06-14 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Systèmes microfluidiques numériques pour manipuler des gouttelettes
EP3887814A4 (fr) * 2018-12-02 2022-08-24 Polymer Technology Systems, Inc. Systèmes et méthodes destinés à une caractéristique de grille électronique dans une bande de test électrochimique

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9638685B2 (en) 2014-09-19 2017-05-02 Tokitae Llc Flow assay with at least one electrically-actuated fluid flow control valve and related methods
US10549273B2 (en) 2014-09-19 2020-02-04 Tokitae Llc Flow assay with at least one electrically-actuated fluid flow control valve and related methods
GB2542372A (en) * 2015-09-16 2017-03-22 Sharp Kk Microfluidic device and a method of loading fluid therein
US10369567B2 (en) * 2015-11-04 2019-08-06 International Business Machines Corporation Continuous, capacitance-based monitoring of liquid flows in a microfluidic device
WO2018187535A1 (fr) * 2017-04-07 2018-10-11 Tokitae Llc Dispositif d'analyse d'écoulement comprenant au moins une vanne de commande de débit à actionnement électrique et procédés associés
EP3858484A1 (fr) * 2020-02-03 2021-08-04 Vrije Universiteit Brussel Inducteur de vortex de silicium sur isolant structuré sur puce
CN113649089A (zh) * 2021-07-16 2021-11-16 法国介观生物技术有限公司 一种微流控芯片
CN115337968B (zh) * 2022-08-13 2023-08-18 兰州大学 一种基于slips绝缘疏水膜的半封闭数字微流控系统

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000044930A1 (fr) * 1999-01-28 2000-08-03 Abbott Laboratories Teste diagnostique pour la mesure d'analyte dans un liquide corporel
WO2011131795A1 (fr) * 2010-04-23 2011-10-27 Celoxio Ab Systèmes microfluidiques comprenant des commutateurs de mouillabilité électroniques

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8349276B2 (en) * 2002-09-24 2013-01-08 Duke University Apparatuses and methods for manipulating droplets on a printed circuit board
US6911132B2 (en) * 2002-09-24 2005-06-28 Duke University Apparatus for manipulating droplets by electrowetting-based techniques
US8037903B2 (en) * 2007-04-04 2011-10-18 Micropoint Bioscience, Inc. Micromachined electrowetting microfluidic valve

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000044930A1 (fr) * 1999-01-28 2000-08-03 Abbott Laboratories Teste diagnostique pour la mesure d'analyte dans un liquide corporel
WO2011131795A1 (fr) * 2010-04-23 2011-10-27 Celoxio Ab Systèmes microfluidiques comprenant des commutateurs de mouillabilité électroniques

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
SATOH WATARU ET AL: "Microfluidic transport based on direct electrowetting", JOURNAL OF APPLIED PHYSICS, AMERICAN INSTITUTE OF PHYSICS. NEW YORK, US, vol. 96, no. 1, 1 July 2004 (2004-07-01), pages 835 - 841, XP012068064, ISSN: 0021-8979, DOI: 10.1063/1.1739528 *
TSUKUBA: "Japan in the article Microfluidic transport based on direct electrowetting", J. APPL. PHYS., vol. 96, 2004, pages 835

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018106750A1 (fr) * 2016-12-08 2018-06-14 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Systèmes microfluidiques numériques pour manipuler des gouttelettes
EP3887814A4 (fr) * 2018-12-02 2022-08-24 Polymer Technology Systems, Inc. Systèmes et méthodes destinés à une caractéristique de grille électronique dans une bande de test électrochimique

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US20150204817A1 (en) 2015-07-23
ES2644613T3 (es) 2017-11-29
EP2893348B1 (fr) 2017-07-26
US10309926B2 (en) 2019-06-04
EP2893348A1 (fr) 2015-07-15

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